Transplantation of syngeneic islets can reverse experimental diabetes in inbred, laboratory rodents. Although significant progress has been made in the techniques of immunosurpression, the phenomenon of immune rejection still prevents the application of these research findings to the amelioration of human diabetes. The cerebral ventricles have been shown to be a privileged site for the transplantation of many tissues; immune rejection of the transplanted tissue is delayed or even absent. We propose to transplant isolated pancreatic islets to the cerebral ventricles of alloxan diabetic synergic and allogeneic hosts. The syngeneic transplants will be used to establish the protocol by which the islets transplanted to the ventricles can result in the reversal of the diabetic state. The allogeneic transplants will be used to examine the ability of islets in the ventricles to avoid immune rejection. Finally, we propose to define the roles of donor islet age (fetal or neonatal), the number of islets transplanted, and the period of tissue culture prior to transplantation of the reversal of experimental diabetes using this site. This technique may be directly applicable for use in the treatment of human diabetes.